This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There are 43 BTB-ZF and 49 BTB-BACK-Kelch (BBK) proteins in humans (Stogios et al 2005). The BTB-ZF proteins have a single N-terminal BTB domain, an intrinsically disordered middle region and a set of C terminal zinc-finger (ZF) domains. Similarly, the BBK proteins have a single N-terminal BTB domain, a central BACK domain (Stogios and Priv[unreadable] 2004) and C-terminal Kelch repeats. In general, all BTB-ZF proteins are transcription factors, and the BBK proteins are substrate binding adaptors in Cullin3-based E3 ubiquitin ligase complexes. BTB-ZF proteins: We have solved a total of 9 crystal structures of BTB domains from BTB-ZF proteins (Ghetu et al 2008;Stogios et al 2007, Ahmad et al 2003, etc). These are either homodimers or hexamers, implying that the transcription factors are either bivalent or hexavalent. We are now moving towards studying the full-length proteins by SAXS in order to understand the topological arrangement of the DNA binding ZF domains within the full-length proteins, possibly in complex with DNA fragments. BBK proteins are elongated dimeric and/or tetrameric proteins that interact with Cul3 at the BTB end and substrate at the Kelch end, resulting in the ubiquitination of substrate in Cul3-based SCF-like E3 ligase complexes (Pintard et al 2004). E3 ligase complexes are widely studied, but the issue of the oligomeric state of these complexes is poorly understood. BBK proteins oligomerize via their BTB domains, and we have in-house solution data showing both 2:2 and 4:4 BBK/Cul3 complexes.